This pilot clinical trial studies how well imetelstat sodium works in treating patients with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:

MF patients: Overall response rate defined as a clinical improvement (CI), partial remission (PR), or complete remission (CR) according to the IWG-MRT consensus criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Will be estimated by the number of successes divided by the total number of evaluable patients.

MDS patients: Overall response rate according to the IWG response criteria in myelodysplasia [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Will be estimated by the number of successes divided by the total number of evaluable patients.

Secondary Outcome Measures:

Maximum grade for each type of adverse event for each patient [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Spleen response defined as either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not palpable [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Will be calculated by the number of patients who achieve spleen response divided by the total number of evaluable patients with spleen involvement at baseline (estimated to be approximately 80% of patients).

Proportion of patients achieving transfusion independence [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Will be estimated by the number of patients who achieve transfusion independence divided by the total number of evaluable patients who were transfusion dependent at baseline.

Myelofibrosis (MF) participants will receive Imetelstat, 9.4 milligram per kilogram (mg/kg), intravenously [IV] as 2 hour infusion, on Day 1 of every 21-day cycle up to 3 years until disease progression or unacceptable toxicity.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Experimental: Arm B

MF participants will receive Imetelstat, 9.4mg/kg, IV as 2 hour infusion, on Day 1, 8, 15 of Cycle 1, then Day 1 of each subsequent 21-day cycle up to 3 years until disease progression or unacceptable toxicity.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Experimental: Arm D

Blast phase MF participants will receive Imetelstat, 9.4mg/kg, IV as 2 hour infusion, on Day 1, 8, 15, 22 of every 28-day cycle up to 3 years until disease progression or unacceptable toxicity.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Experimental: Arm E

MF participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 7.5mg/kg, IV as 2 hour infusion, on Day 1 of every 28-day cycle.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Experimental: Arm F

MF participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 9.4mg/kg on Day1 of every 28-day cycle.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Experimental: Arm G

Myelodysplastic syndromes (MDS)/ myeloproliferative neoplasm (MPN) or MDS participants with spliceosome mutations or ring sideroblasts will receive Imetelstat, 7.5mg/kg on Day 1 of every 28-day cycle.

Drug: Imetelstat

Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose and schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication as per arms.

Other Name: GRN163L

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate overall response rate.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis (MF).

II. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by physical examination (palpable distance from the left costal margin).

III. To evaluate the efficacy of imetelstat in improving anemia or inducing red blood cell transfusion-independence in previously transfusion-dependent patients (per International Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria).

IV. To evaluate onset and durability of response as defined in primary and secondary endpoints

Absence of active treatment with systemic anticoagulation and a baseline prothrombin time (PT) and activated partial thromboplastin time (aPTT) that does not exceed 1.5 x ULN

Females of childbearing potential must have a negative pregnancy test =< 7 days prior to registration, unless they are surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (follicle-stimulating hormone [FSH] >30 U/mL)

Females of childbearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study; permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed

Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up; permitted methods for preventing pregnancy should be communicated to the subjects and their understanding confirmed

Note: patients with early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin or cervical intraepithelial neoplasia are eligible for enrollment

Known positive status for human immunodeficiency virus (HIV)

Any unresolved toxicity greater or equal to grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve

Incomplete recovery from any prior surgical procedures or had surgery =< 4 weeks prior to registration, excluding the placement of vascular access

Presence of acute active infection requiring antibiotics

Uncontrolled intercurrent illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01731951